Red hair link to Parkinson’s disease

Iain Lynn

Ginger haired people are more likely to develop Parkinson's disease, according to new research.

A gene mutation that produces red locks and fair skin may explain the link between skin cancer and the devastating neurological illness.

The breakthrough could lead to a new drug that targets the protein. Parkinson's affects about 127,000 people in the UK. There is currently no cure.

A study found mice carrying the variant MC1R (melanocortin 1 receptor) produced less dopamine in the substantia nigra.

Parkinson's is caused by loss of neurons in this area of the brain that make this chemical that controls movement.

Symptoms

The main symptoms are tremor, muscle stiffness and slowness. Mutated versions of MC1R also trigger melanoma, the deadliest form of skin cancer.

Study leader Professor Xiqun Chen, of the Massachusetts General Institute for Neurodegenerative Disease, said: "This study is the first to show direct influences of the melanoma-linked MC1R gene on dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a novel therapeutic strategy for Parkinson's disease.

"It also forms a foundation for further interdisciplinary investigations into the dual role of this gene in the growth of tumours within melanocytes - the pigment cells in which melanoma develops - and the degeneration of dopaminergic neurons, improving our understanding of why and how melanoma and Parkinson's disease are linked."

The substantia nigra is the brain structure in which dopamine producing neurons are destroyed in Parkinson's disease. They are more susceptible to toxins known to damage those neurons.

Nerve cells

The disease is caused by the loss of nerve cells in the brain that produce the dopamine, which also helps to control mood as well as movement.

The gene variant MC1R produces red hair and fair skin in humans and in mice, which increases the risk of melanoma.

The latest finding published in Annals of Neurology suggests it also contributes to the known link between melanoma and Parkinson's.

Inherited mutations of MC1R determine skin pigmentation, with the most common form leading to greater production of the darker colour called eumelanin and the 'red hair gene'.

The latter inactivates the gene's function, increasing production of the lighter pigment called pheomelanin.

This chemical provides less protection from ultraviolet damage to the skin than does eumelanin.

In 2012 research by dermatologist Dr David Fisher, a co author of the current study, found it may also directly contribute to melanoma development.

Cancer risk

Interestingly, patients with Parkinson's have a reduced risk of developing most types of cancer, apart from melanoma, which is well recognised to be higher.

Likewise, patients with melanoma are more likely to develop Parkinson's. Several recent studies have also found evidence suggesting increased Parkinson's risk in individuals with the red hair gene.

So Dr Chen and colleagues decided to explore that potential role of the gene in Parkinson's, and specifically in dopamine producing neurons of the substantia nigra.

In red haired mice the gene is inactivated because of the mutation. They were found to have fewer dopamine-producing neurons and as they aged, developed a progressive decline in movement and a drop in levels of the chemical.

They were more sensitive to toxic substances known to damage dopamine-producing neurons.

And they also had increased oxidative stress - which the 2012 study implied was involved in melanoma risk - in brain areas next to the substantia nigra.

Treatment with a substance that boosts MC1R signalling reduced the susceptibility to a neurotoxin, further supporting a protective role for the gene's activity.

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